Biomedical subjects

R Meagher

Publications and source records attributed to R Meagher.

7 recordsLinked to original sources

PubMed2006

Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?

Sixty three patients aged 27-66 years (median 52) were allografted from HLA-matched sibling (n=47), 10 of 10 allele-matched unrelated (n=19), or one-antigen/allele-mismatched (n=7) donors aged 24-69 years (median 46) after a conditioning regimen comprising 100 mg/m(2) melphalan. Cyclophosphamide (50 mg/kg) was also administered to patients who had not been autografted previously. Cyclosporine or tacrolimus, and mycophenolate mofetil were administered to prevent graft-versus-host disease (GVHD). The 2-year cumulative incidences of relapse and TRM were 55 and 24% respectively, and 2-year probabilities of overall survival (OS) and disease-free survival (DFS) were 36 and 21%, respectively. Poor performance status, donor age >45 years and elevated lactate dehydrogenase (LDH) increased the risk of treatment-related mortality (TRM), refractory disease and donor age >45 years increased the risk of relapse, and OS and DFS were adversely influenced by refractory disease, poor performance status, increased LDH, and donor age >45 years. Our data suggest that younger donor age is associated with better outcome after sub-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies due to lower TRM and relapse. This finding raises the question of whether a young 10-allele-matched unrelated donor is superior to an older matched sibling donor in patients where the clinical situation permits a choice between such donors.

Adult↗

PubMed2006

Ideal rather than actual body weight should be used to calculate cell dose in allogeneic hematopoietic stem cell transplantation.

Whether the CD34+ and CD3+ cell doses in allogeneic HSCT should be estimated using actual (ABW) or ideal (IBW) body weight has never been definitively determined. We have shown that CD34+ cell doses based upon IBW are better predictive of engraftment after autologous and allogeneic HSCT. Sixty-three patients undergoing reduced-intensity HSCT after a uniform preparative regimen were evaluated to determine the effect of cell dose. ABW and IBW were 45-147 kg (median 79) and 52-85 kg (median 67) respectively. The ABW-IBW difference was -24% to +133% (median +16%); nine patients were >5% underweight and 41 were >5% overweight. The CD34+ cell dose (10(6)/kg) was 1.4-11.8 (median 5) by IBW and 1.2-9.3 (median 4.5) by ABW. The CD3+ cell dose (10(8)/kg) was 0.9-14.9 (median 3) by IBW and 0.7-19.7 (median 2.7) by ABW. While CD34+ and CD3+ cell doses based upon IBW were found to affect transplant-related mortality, and disease-free and overall survival significantly, those based on ABW were either not predictive of outcome or the differences were of borderline significance. We suggest using IBW rather than ABW to calculate cell doses for HSCT; for statistical analyses and for clinical practice if a specific cell dose is being targeted.

Adult↗

PubMed2003

Fall armyworm FR sequences map to sex chromosomes and their distribution in the wild indicate limitations in interstrain mating.

The fall armyworm, Spodoptera frugiperda, consists of two host strains (rice and corn) that differ in developmental, physiological and behavioural characteristics. However, because the strains are morphologically indistinguishable the investigation of strain-specific behaviour, particularly in the wild, is very difficult. This has spurred the isolation of diagnostic molecular markers. FR sequences are tandem-repeat genetic elements found in large clusters only in the rice strain. To facilitate their use as a strain marker we genetically mapped FR clusters and found they localized to the sex chromosomes. This represents one of the first examples of chromosome mapping in fall armyworm. The FR sequence and a strain-specific mitochondrial marker were then used to examine the distribution of different marker combinations in field specimens. These studies identified significant barriers to interstrain mating in the wild, specifically that corn strain females rarely, if ever, mate with rice strain males. The data also suggest that only a genetically distinct subset of the overwintering rice strain population in Florida annually migrate to Georgia. These studies demonstrate that the availability of genetically characterized molecular markers for strain identity makes possible studies on fall armyworm biology in the wild previously considered unfeasible.

Animals↗

PubMed1999

Ex vivo expansion of CD34+ umbilical cord blood cells in a defined serum-free medium (QBSF-60) with early effect cytokines.

To investigate the clinically applicable conditions that support substantial expansion of both primitive and more mature hematopoietic cells of umbilical cord blood (UCB) for transplantation in adults, enriched CD34+ cells from 8 fresh UCB samples and 4 expanded UCB products were cultured in defined serum-free medium (QBSF-60) in the presence of a cytokine combination of SCF, Flt-3-ligand (FL), thrombopoietin (TPO), IL-3 for up to 2 weeks. Fresh medium with cytokines was supplemented or exchanged at day 4, day 7, and day 10. The proliferative response was assessed at day 7, day 10, and day 14 by evaluating the following parameters: nucleated cell (NC), clonogenic progenitors (colony-forming unit-granulocyte-macrophage [CFU-GM], burst-forming unit-erythrocyte [BFU-E], CFU-GEMM, and high-proliferative potential colony-forming cell [HPP-CFC]), immunophenotypes (CD34+ cells and CD34+ subpopulations), and LTCIC. Simultaneously numerical expansion of various stem/progenitor cells, including primitive CD34+CD38-HLA-DR- subpopulation and LTCIC, CD34+ cells, and clonogenic progenitors to mature nucleated cells, were continuously observed during the culture. An average 103.32 +/- 71.37 x 10(6) CD34+ cells (range 10.12 x 10(6)-317.9 x 10(6)) could be obtained from initial 1.72 +/- 1.13 x 10(6) UCB CD34+ cells after 10-14 days cultured under the described conditions. Sufficient CD34+ cells (>50.0 x 10(6)) for transplantation in adults would be available in all but one UCB collections after 10-14 days expansion. The expanded CD34+ cells sustained most of the in vitro characteristics of initial unmanipulated CD34+ cells, including clonogenic efficiency (of both primitive and committed progenitors), the proportion of CD34+CD38-HLA-DR- subpopulation, and the expansion potential. Initial addition of IL-3 to the cocktail of SCF + FL + TPO had positive effects on the expansion of both primitive and, especially, the more mature hematopoietic cells. It accelerated the expansion speed and shortened the optimal culture time from 14 days to 10 days. These results indicated that our proposed short-term culture system, consisting of QBSF-60 serum-free medium with a simple early acting cytokine combination of SCF + FL + TPO, could substantially support simultaneous expansion of various stem/progenitor cell populations involved in the different phases of engraftment. It would be a clinically applicable protocol for ex vivo expansion of CD34+ UCB cells.

Antigens, CD34↗

PubMed1990

Placental CSF-like activity.

We have examined amniotic fluid and cultured supernatants of a variety of placental cells for the presence of colony-stimulating factor (CSF) activity. The supernatants of cultured human choriocarcinoma cell lines, Jeg and Jar, contained CSF activity that induced the formation of granulocyte-macrophage colony-forming unit (CFU-GM) and multipotential colony-forming unit (CFU-GEMM) colonies. Cultured supernatants of nontransformed rat placental cells, chorionic villous cells, and amniotic fluid also induced CFU-GM colonies.

Amniotic Fluid↗

PubMed1980

Measuring racial bias in inpatient treatment.

In a retrospective chart audit of 66 black and 36 white male schizophrenic inpatients, the authors found that black patients spent less time in the hospital, obtained a lower privilege level, were given more p.r.n. medications, and were less likely to receive recreation therapy and occupational therapy. Seclusion and restraints were more likely to be used with black patients. The authors ruled out the possibility of more severe pathology in the black patients by global rating of an additional 15 white and 15 black patients. Concluding that there was racial bias, they attribute it to subtle stereotyping and the staff's greater familiarity with white patients; they suggest increased recruitment of black professionals and the inclusion of blacks in each treatment team.

Adult↗

PubMedDate not supplied

Mechanisms underlying the suppression of erythropoiesis by hyperoxia.

The possible mechanisms underlying the suppression of erythropoiesis in hyperoxic animals were studied. Male Long-Evans rats were injected with cobaltous chloride hexahydrate, a known erythropoietic stimulant. One group was exposed to a hyperoxic environment for ten hours. Both serum levels of erythropoietin (Ep) and renal levels of erythrogenin were significantly lower (p less than 0.005) in the hyperoxic animals compared to those left at room air. In addition, inhibitors to Ep or erythrogenin could not be detected in either the serum or renal tissue of the hyperoxic rats. These results indicate that the primary factor responsible for the erythropoietic suppression observed in a hyperoxic environment is a decreased production of erythrogenin which results in turn, in a lowered level of circulating Ep.

Animals↗